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Run-down of the GABAA response under experimental ischaemia in acutely dissociated CA1 pyramidal neurones of the rat
Journal article   Open access   Peer reviewed

Run-down of the GABAA response under experimental ischaemia in acutely dissociated CA1 pyramidal neurones of the rat

N Harata, Jie Wu, H Ishibashi, K Ono and Norio Akaike
The Journal of physiology, Vol.500 ( Pt 3)(Pt 3), pp.673-688
05/01/1997
DOI: 10.1113/jphysiol.1997.sp022052
PMCID: PMC1159418
PMID: 9161985
url
https://doi.org/10.1113/jphysiol.1997.sp022052View
Published (Version of record) Open Access

Abstract

1. The effect of experimental ischaemia on the response to gamma-aminobutyric acid (GABA) was assessed in acutely dissociated CA1 pyramidal neurones of rats, using the patch-clamp technique. 2. Rapid application of 3 x 10(-5) M GABA induced a bicuculline-sensitive inward Cl- current (IGABA) at a holding potential (Vh) of -44 mV. The peak amplitude of IGABA showed a time-dependent decrease (run-down) when it was recorded with the conventional whole-cell mode without internal ATP. The run-down was not observed when the intracellular ATP concentration ([ATP]i) was maintained by the nystatin-perforated recording with an intracellular Na+ concentration ([Na+]i) of 0 mM. 3. When [Na+]i was increased to more than 30 mM, the IGABA run-down was observed even with the nystatin-perforated recording. 4. The IGABA run-down observed at 60 mM [Na+]i with the nystatin method was further enhanced under experimental ischaemia without changes in the reversal potential of IGABA. The enhanced run-down was suppressed by application of the Na+,K(+)-ATPase inhibitors, ouabain and SPAI-1. 5. IGABA run-down during ischaemia was also accompanied by an outward holding current and a concomitant increase in intracellular free Ca2+ concentration ([Ca2+]i) in 48.5% of the neurones. The outward current was a Ca(2+)-activated K+ current, which was blocked by 3 x 10(-7) M charybdotoxin. 6. In the inside-out mode of the single-channel analysis, GABA activated three subconductance states with conductances of 33.4, 22.7 and 15.2 pS. Reduction of ATP concentration from 2 to 0 mM on the intracellular side suppressed the channel activities, while an increase in Ca2+ concentration from 0.7 x 10(-9) to 1.1 x 10(-6) M had no effect. 7. These results suggest that ischaemia induces the run-down of the postsynaptic GABA response at the GABAA receptor level, and that this run-down is triggered by a decrease in [ATP]i.
 Electrophysiology Sodium - pharmacology Chloride Channels - drug effects Rats, Wistar Calcium - metabolism Rats Brain Ischemia - physiopathology Membrane Potentials - physiology Ionophores Chloride Channels - metabolism Sodium-Potassium-Exchanging ATPase - metabolism Patch-Clamp Techniques Animals Pyramidal Cells - physiology Receptors, GABA-A - physiology Second Messenger Systems - physiology Adenosine Triphosphate - physiology In Vitro Techniques Nystatin

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